RB--this one's for you!

[Lani]

Cancer Res. 2008 Apr 15;68(8):2912-9.

Peroxisome proliferator-activated receptor gamma-mediated up-regulation of syndecan-1 by n-3 fatty acids promotes apoptosis of human breast cancer cells.

Sun H, Berquin IM, Owens RT, O'Flaherty JT, Edwards IJ.
Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Diets enriched in n-3 polyunsaturated fatty acids (n-3 PUFA) may protect against breast cancer but biochemical mechanisms are unclear. Our studies showed that the n-3 fatty acid docosahexaenoic acid (DHA) up-regulated syndecan-1 (SDC-1) in human breast cancer cells, and we tested the hypothesis that DHA-mediated up-regulation of SDC-1 induces apoptosis. DHA was delivered to MCF-7 cells by n-3 PUFA-enriched low-density lipoproteins (LDL) or by albumin in the presence or absence of SDC-1 small interfering RNA. The n-3 PUFA induced apoptosis, which was blocked by SDC-1 silencing. We also confirmed that SDC-1 up-regulation and apoptosis promotion by n-3 PUFA was mediated by peroxisome proliferator-activated receptor gamma (PPAR gamma). Using a luciferase gene driven by either a PPAR response element or a DR-1 site present in the SDC-1 promoter, reporter activities were enhanced by n-3 LDL, DHA, and PPAR gamma agonist, whereas activity of a luciferase gene placed downstream of a mutant DR-1 site was unresponsive. Cotransfection with dominant-negative PPAR gamma DNA eliminated the increase in luciferase activity. These data provide strong evidence that SDC-1 is a molecular target of n-3 PUFA in human breast cancer cells through activation of PPAR gamma and that n-3 PUFA-induced apoptosis is mediated by SDC-1. This provides a novel mechanism for the chemopreventive effects of n-3 PUFA in breast cancer.
PMID: 18413760 [PubMed - in process]

[R.B.]

Thank you Lani for posting.

I know nothing about sdc1.

More things to look up when I time.

A very quick sacn produced this.


http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum

Anticancer Res. 2007 Sep-Oct;27(5A):3045-50.Links
Expression of syndecan-1 in paired samples of normal and malignant breast tissue from postmenopausal women.
Lofgren L, Sahlin L, Jiang S, Von Schoultz B, Fernstad R, Skoog L, Von Schoultz E.

Department of Surgery, St Görans Hospital, Karolinska University Hospital, Stockholm, Sweden. lars.lofgren@capio.se

BACKGROUND: The mammary stroma is important for modulating epithelial breast cell response to sex steroid hormones. Proteoglycans, such as syndecan-1, promote the integration of cellular signals. MATERIALS AND METHODS: The immunohistochemical expression of syndecan-1 and of the androgen receptor (AR) was analyzed in paired samples of cancer and adjacent normal tissue from postmenopausal women. RESULTS: Normal and cancer tissue showed dramatic differences in the expression of syndecan-1. In malignant breast stroma, mean values were more than 10-fold higher than in normal tissue (p<0.001). There was also a marked redistribution from the epithelium to the stroma. The expression of AR was on average 2-fold higher in cancerous than in normal tissue (p<0.01). CONCLUSION: Breast cancer patients have very different prognoses. Syndecan-1 and the AR may be new molecular markers relevant to clinical outcome. The redistribution from the epithelium and the dramatic increase of syndecan-1 in cancerous stroma may be related to the natural history of the disease.